Michael K. Hehir

Introduction/Aims: The Adverse Event Unit (AEU) is a patient and physician weighted unit that quantifies and compares adverse event (AE) burden among any neurologic treatments. A recent study demonstrated feasibility and preliminary validity of the AEU in myasthenia gravis (MG). This study evaluated feasibility of assigning AEU scores retrospectively from pre‐existing data in the randomized clinical trial of thymectomy in MG (MGTX) and quantifying AE burden differences in participants.Methods: Serious and non‐serious AE were recorded at MGTX visits. AEU scores were assigned by matching MGTX AE to AEU categories. Total AEU score for each participant was compared to the prednisone dosage area under the curve for years 1, 2, and 3. We also compared differences in AEU scores between participants treated with prednisone and azathioprine versus those treated with prednisone alone.Results: All 117 MGTX patients received prednisone; 32% also received azathioprine. A weak correlation between increasing prednisone exposure and total AEU score was observed at year 2 (r = 0.19, p = 0.04) and year 3 (r = 0.23, p = 0.01). Participants treated with azathioprine in addition to prednisone had higher AEU scores than patients treated with prednisone alone at years 1 (median AEU 19 vs. 5, p = 0.037), 2 (median AEU 23 vs. 6, p = 0.018), and 3 (median AEU 34 vs. 9, p = 0.006).Discussion: Pre‐existing clinical trial data can be translated into AEU scores. MG patients treated with multiple immunosuppressants had the highest AEU scores, similar to our prospective trial. Future studies will compare the side effect burden of MG treatments and define clinically meaningful AEU scores.

Introduction/Aims: Myasthenia gravis (MG) specific outcome measures are being used in clinical trials to evaluate therapeutic effectiveness. These validated tools are also becoming a necessity in clinical practice, with payors in the US market often requiring them to be used to monitor disease state. There is considerable variation and subjectivity regarding their use. This study aimed to develop consensus‐based recommendations for the standardization of MG specific outcome measures in clinical practice.Methods: A panel of 10 US‐based MG specialists developed consensus‐based recommendations based on three rounds of formal voting using the UCLA‐RAND appropriateness method after surveying myasthenia gravis clinicians and developing a focus group.Results: Twenty one expert consensus statements based on six themes were developed following clinician survey result review and focus group theme development. Some key recommendations include: the MGFA Clinical Classification assesses disease at that examination and should be updated at intervals of 3–6 months to reflect current clinical status. MGFA PIS represents the overall clinical judgment of the evaluator without the requirement for a defined change in scores on any outcome measure. Patient‐reported items, such as MG‐ADL and MGC, should be referenced to the previous 1 week to optimize recall. Additional recommendations include scoring outcome measures in the presence of co‐morbidity, scoring specific physical exam findings, and clarification regarding the administration of outcome measures.Discussion: This method provided expert consensus‐based recommendations for the use of MG‐specific outcome measures and exam findings to help standardize how they are used in clinical practice.

Epidemiologic studies suggest increasing incidence and prevalence of myasthenia gravis (MG) among the elderly population outside the United States. We aimed to provide an estimation of MG incidence and prevalence and their trend among the Medicare Fee-For-Service (FFS)-covered elderly US population. We performed a retrospective longitudinal study using Medicare claims data (2006-2019). Study-eligible beneficiaries were aged 65 years and older, had at least 1 month of FFS Part A/B coverage, and were without any health maintenance organization insurance coverage. Study-eligible beneficiaries were aggregated into 2-year periods from 2006-2007 through 2018-2019. MG cases were ascertained using a validated algorithm of 2 MG claims within each 2-year period, from 2 outpatient office visits or a combination of 1 inpatient admission and 1 outpatient office visit, separated by ≥ 28 days. Period prevalence was calculated from MG-ascertained cases divided by FFS Part A/B beneficiaries and reported as cases per 100,000 population. Incident cases were determined among MG prevalent cases if the initial MG claim occurred in that period after a full calendar year since coverage initiation. Incidence was calculated as case counts per 100,000 at-risk beneficiary person-years (PYs) in each period excluding 2006-2007. Trends of prevalence and incidence over time were examined with Poisson regression. All-cause mortality of each 2-year period was calculated. The period prevalence of MG increased from 81 to 119 per 100,000 FFS A/B population from 2006-2007 to 2018-2019 (p < 0.001). Increasing trends of prevalence were observed in all sex (male/female), age (65-69/70-74/75-79/80+), race/ethnic (African American/Asian/Hispanics of any race/non-Hispanic White/other), and census region (Northeast/Midwest/South/West) subgroups. MG incidence increased from 12.2 to 13.3 per 100,000 PYs from 2008-2009 to 2018-2019 (p < 0.05). Increasing incidence trends were significant in the following subgroups: men and women; all age groups except 75-79 years; White non-Hispanic race; Northeast, Midwest, and South census regions. All-cause mortality among MG beneficiaries was stable from 6.26 deaths per 100 PYs in 2006-2007 to 5.67 in 2018-2019 (p = 0.18). Increasing trends in MG prevalence and incidence in the elderly US population, with variation in rates of certain subgroups, are confirmed in this 14-year period.

Generalized myasthenia gravis (gMG) is a postsynaptic neuromuscular junction disorder that results in fatigable muscle weakness. The traditional treatment approach includes the use of acetylcholinesterase inhibitors, corticosteroids, and steroid‐sparing immunosuppressant therapies (ISTs) for chronic management, whereas exacerbations and crises are managed with intravenous immunoglobulin (IVIg) and plasma exchange (PLEX). Over the past 6 years, four new therapeutic agents with novel immunological mechanisms of action—complement and neonatal Fc receptor (FcRn) inhibition—were approved as a result of clinically significant improvement in gMG symptoms of those treated with these newer agents in Phase 3 clinical trials. At present, it is unclear when and in whom to initiate these therapeutic agents and how to integrate them into the current treatment paradigm. When selecting a newer therapeutic agent, we use a simple equation: Value = Clinical Improvement/(Cost + Side Effects + Treatment Burden), which guides our decision‐making. We consider using these novel therapeutic agents in two specific clinical situations. Firstly, the newer agents are fast‐acting, suggesting they can be used in clinically unstable patients as “bridge therapy,” and secondly, they provide additional options for those patients considered treatment‐refractory. There are downsides, however, including treatment cost, unique side effect profiles, and intravenous and subcutaneous drug administration (though for some, this may be an advantage). As additional drugs enter the marketplace with unique mechanisms of action, routes of administration, and dosing schedules, the placement of the novel therapeutic agents in the gMG treatment algorithm will likely evolve.